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Background: Nitrates and nitrites occur naturally in water and soil. They are also used as food additives (preservatives) in processed meats. They could play a role in the carcinogenicity of processed meat. The objective was to investigate the relationship between nitrate and nitrite intakes (natural food, water and food additive sources) and cancer risk in a large prospective cohort with detailed dietary assessment., Methods: Overall, 101    056 adults from the French NutriNet-Santé cohort (2009-ongoing, median follow-up 6.7 years) were included. Nitrites/nitrates exposure was evaluated using repeated 24-h dietary records, linked to a comprehensive composition database and accounting for commercial names/brands of industrial products. Associations with cancer risk were assessed using multi-adjusted Cox hazard models., Results: In total, 3311 incident cancer cases were diagnosed. Compared with non-consumers, high consumers of food additive nitrates had higher breast cancer risk [hazard ratio (HR) = 1.24 (95% CI 1.03-1.48), P = 0.02], more specifically for potassium nitrate. High consumers of food additive nitrites had higher prostate cancer risk [HR = 1.58 (1.14-2.18), P = 0.008], specifically for sodium nitrite. Although similar HRs were observed for colorectal cancer for additive nitrites [HR = 1.22 (0.85-1.75)] and nitrates [HR = 1.26 (0.90-1.76)], no association was detected, maybe due to limited statistical power for this cancer location. No association was observed for natural sources., Conclusion: Food additive nitrates and nitrites were positively associated with breast and prostate cancer risks, respectively. Although these results need confirmation in other large-scale prospective studies, they provide new insights in a context of lively debate around the ban of these additives from the food industry., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Food additives (e.g. artificial sweeteners, emulsifiers, dyes, etc.) are ingested by billions of individuals daily. Some concerning results, mainly derived from animal and/or cell-based experimental studies, have recently emerged suggesting potential detrimental effects of several widely consumed additives. Profiles of additive exposure as well as the potential long-term impact of multiple exposure on human health are poorly documented. This work aimed to estimate the usual intake of food additives among participants of the French NutriNet-Santé cohort and to identify and describe profiles of exposure (single substances and mixtures). Overall, 106,489 adults from the French NutriNet-Santé cohort study (2009-ongoing) were included. Consumption of 90 main food additives was evaluated using repeated 24 h dietary records including information on brands of commercial products. Qualitative information (as presence/absence) of each additive in food products was determined using 3 large-scale composition databases (OQALI, Open Food Facts, GNPD), accounting for the date of consumption of the product. Quantitative ingested doses were estimated using a combination of laboratory assays on food matrixes (n = 2677) and data from EFSA and JECFA. Exposure was estimated in mg per kg of body weight per day. Profiles of exposure to food additive mixtures were extracted using Non-negative Matrix Factorization (NMF) followed by k-means clustering as well as Graphical Lasso. Sociodemographic and dietary comparison of clusters of participants was performed by Chi-square tests or linear regressions. Data were weighted according to the national census. Forty-eight additives were consumed by more than 10% of the participants, with modified starches and citric acid consumed by more than 90%. The top 50 also included several food additives for which potential adverse health effects have been suggested by recent experimental studies: lecithins (86.6% consumers), mono- and diglycerides of fatty acids (78.1%), carrageenan (77.5%), sodium nitrite (73.9%), di-, tri- and polyphosphates (70.1%), potassium sorbate (65.8%), potassium metabisulphite (44.8%), acesulfame K (34.0%), cochineal (33.9%), potassium nitrate (31.6%), sulfite ammonia caramel (28.8%), bixin (19.5%), monosodium glutamate (15.1%) and sucralose (13.5%). We identified and described five clusters of participants more specifically exposed to five distinct additive mixtures and one additional cluster gathering participants with overall low additive exposure. Food additives, including several for which health concerns are currently debated, were widely consumed in this population-based study. Furthermore, main mixtures of additives were identified. Their health impact and potential cocktail effects should be explored in future epidemiological and experimental studies., (© 2021. The Author(s).)